Pyridine → HCID 59596669, compound

HRID 2264802Notes

Reaction equation

HRID 2264802 reaction equation
[NH2:1][C:2]([C@@H:4]1[CH2:8][CH2:7][C@H:6]([C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)[N:5]1[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[O:3].[F:23][C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1.N1C=CC=CC=1.C(N(CC)CC)C>C(Cl)Cl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[NH2:1][C:2]([C@@H:4]1[CH2:8][CH2:7][C@H:6]([C:9]2[CH:14]=[CH:13][C:12]([O:15][C:27]3[CH:28]=[CH:29][C:24]([F:23])=[CH:25][CH:26]=3)=[CH:11][CH:10]=2)[N:5]1[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[O:3]

Participants

7

Reactant 4

HCID 1049PyridineHCID 8471TriethylamineHCID 2856454-Fluorophenylboronic acidHCID 59164822HCID 59164822, compound

Product 1

HCID 59596669HCID 59596669, compoundYield 112.8%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

This compound was prepared in two batches under different conditions (Conditions A and B). In a closed vial 1,1-dimethylethyl (2S,5R)-2-(aminocarbonyl)-5-(4-hydroxyphenyl)-1-pyrrolidinecarboxylate (D13, 19 mg, 0.062 mmol), copper-(II)-acetate (11 mg, 0.062 mmol), (4-fluorophenyl)boronic acid (17 mg, 0.124 mmol) and molecular sieves were suspended in DCM. Then either pyridine (Condition A, 24.5 mg, 0.31 mmol) or triethylamine (Condition B, 31.3 mg, 0.31 mmol) was added and the reaction was shaken at room temperature for 24 h. The crude reaction products from Conditions A and B were combined, filtered and evaporated. The crude residue was purified by chromatography on silica gel using cyclohexanes/ethyl acetate (7:3) to afford the title compound (28 mg, 56%); Rt (HPLC): 5.61 min; MS: (ES/+) m/z: 423 [M+Na+], C22H25N2O4 requires 400; 1H NMR (400 MHz, DMSO-d6) δ ppm: 1.08 (s, 9H); 1.73-1.84 (m, 1H); 1.86-1.96 (m, 1H); 2.00-2.11 (m, 1H); 2.17-2.27 (m, 1H); 4.56-4.73 (m, 1H); 4.74-4.86 (m, 1H); 6.92 (br. s., 2H); 6.95 (br. s., 1H); 7.02 (br. s., 2H); 7.21 (t, 2H); 7.38 (s, 1H); 7.64 (br. s., 2H).

Workup

  1. customThis compound was prepared in two batches under different conditions (Conditions A and B)
  2. customThe crude reaction products from Conditions A and B
  3. filtrationfiltered
  4. customevaporated
  5. customThe crude residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-4d39a913ec3443829c2a3813c609039d
Source dataset
uspto-grants-2010_12
Patent number
US07855218B2

Reaction notes

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